Acute zonal occult outer retinopathy (AZOOR), first described by Gass in 1992, is an idiopathic syndrome with acute outer retinal impairment [
The pathogenesis causing the photoreceptor impairment in AZOOR is still unresolved. Regarding the association between AZOOR and the choroid, abnormalities on indocyanine green angiography (ICGA) have been reported as hypofluorescence in areas related or unrelated to the lesions [
There are only a few reports that evaluated choroidal thickness in AZOOR. Subfoveal choroidal thickness in AZOOR patients tended to be less than that in normal eyes without retinal diseases (243
The aim of this study was to evaluate sequential changes in choroidal thickness at the affected area in eyes with AZOOR.
This retrospective observational case series included 14 affected eyes and 6 unaffected fellow eyes as controls from 10 patients with AZOOR (2 men and 8 women) who visited Hokkaido University Hospital from May 2011 through September 2014. Inclusion criteria were AZOOR eyes showing outer retinal morphological abnormalities in the macular area on OCT at the initial visit, regardless of the types of scotomata, and receiving choroidal thickness measurements with enhanced depth imaging- (EDI-) OCT for up to 6 months after baseline. The current study was approved by the ethics committee of Hokkaido University Hospital and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from each subject after the nature and potential consequences of the study had been explained.
The diagnostic criteria for AZOOR were as follows: acute visual field or vision loss usually with concurrent photopsia; one or more visual field defect regions that could not be explained by funduscopic examination or fluorescein angiography (FA); decreased multifocal ERG responses corresponding to retinal sites with visual field defects; and outer retinal morphologic abnormalities, including absence or discontinuity of the ellipsoid zone and/or the interdigitation zone on OCT [
Of the 10 patients included in this study, 6 patients (9 eyes) who had the best-corrected visual acuity (BCVA) of more than 0.5 at the initial visit with nonprogressive clinical courses or who refused the administration of systemic corticosteroids despite an initially worsened BCVA were followed up without treatment (cases 1–6). Four patients (5 eyes) with an initially worsened BCVA and progressive central or paracentral visual function loss were treated with systemic corticosteroids, including corticosteroid pulse therapy or oral prednisolone (cases 7–10). The regimen for corticosteroid pulse therapy has been described previously [
At the initial visit, each patient underwent thorough ophthalmic examinations including BCVA, indirect ophthalmoscopy, FA, ICGA, 20 J single-flash ERG, and SD-OCT (cross-sectional retinal B-scans of 5 × 5 lines) combined with EDI-OCT (RS-3000 Advance; NIDEK, Gamagori, Japan). Several days later, these examinations were followed by visual field testing (Goldmann perimetry and a Humphrey 30-2 Swedish Interactive Threshold Algorithm (SITA) standard test), fundus autofluorescence, and multifocal ERG. BCVA, Humphrey perimetry, and OCT findings were assessed at baseline as well as at 3 and 6 months after baseline.
EDI-OCT measurements were obtained for each of the evaluation points at the initial visit and 3 and 6 months after the initial visit for nontreated AZOOR patients and before treatment and 3 and 6 months after the start of treatment for AZOOR patients receiving systemic corticosteroids. Using a horizontal scan through the fovea (scan length, 9.0 mm), choroidal thicknesses at the subfovea and at nasal and temporal sites 1000
Photographs of the left eye at the initial visit (a, b, c, and e) and 6 months after the start of systemic corticosteroids therapy (d, f) in a patient (case 9) with acute zonal occult outer retinopathy (AZOOR). (a) Fundus photograph showing a normal retinal appearance. Best-corrected visual acuity (BCVA) was 1.0. (b) Multifocal electroretinography showing a decreased amplitude at the retinal site corresponding to the visual field defect (Figure
Using Humphrey perimetry, 4 adjacent threshold points at the lesion area were selected at the lesion area in the AZOOR eyes (Figures
All results are expressed as the mean ± standard deviation (SD). BCVA was converted to the logarithm of the minimum angle of resolution (logMAR) scale for the purpose of statistical analyses. Mann–Whitney
Table
Clinical characteristics of patients with acute zonal occult outer retinopathy (AZOOR).
Case | Age | Sex | Eye | Medical or ocular history | Duration from onset to first visit (M) | Follow-up duration (M) | Refraction (D) | Goldmann perimetry | Funduscopic findings | Ellipsoid zone | Interdigitation zone | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | 6 M | Baseline | 6 M | ||||||||||
1 | 45 | F | L | Hashimoto’s disease | 4 | 35 | −14.25 | CS + BSE + RS | Myopic macular CRA | − | + | − | ± |
2 | 64 | M | R | None | 6 | 30 | −5.75 | ND | Normal | ± | ± | − | − |
L | −6.00 | ND | Normal | − | ± | − | ± | ||||||
3 | 45 | F | L | None | 0.25 | 28 | 0.00 | BSE + SAS | Normal | + | + | ± | ± |
4 | 28 | F | R | Depression | 3 | 21 | −5.00 | PCC | Normal | + | + | ± | + |
L | −5.25 | PCC + IS | Normal | + | + | ± | + | ||||||
5 | 47 | F | L | Bronchial asthma | 2 | 16 | −0.75 | CS + BSE + IS + SAS | Normal | − | + | − | − |
6 | 17 | F | R | Hashimoto’s disease | 0.25 | 6 | −6.75 | BSE | Normal | ± | + | − | + |
L | −6.75 | BSE + CS | Normal | ± | + | − | + | ||||||
7 | 21 | F | R | None | 0.25 | 39 | −7.50 | CS + BSE | Morning glory optic disc | ± | + | − | ± |
8 | 39 | F | R | Basedow disease | 2 | 33 | −1.25 | CS + BSE + IS | Normal | ± | ± | − | ± |
9 | 57 | M | R | None | 0.25 | 12 | 0.50 | CS + BSE + IS | Normal | ± | + | − | ± |
L | 0.75 | CS + BSE + IS | Normal | ± | + | ± | + | ||||||
10 | 43 | F | L | None | 0.50 | 7 | −4.25 | BSE + STAS | Peripapillary CRA | ± | + | − | ± |
BSE: blind spot enlargement; CRA: chorioretinal atrophy; CS: central scotoma: IS: isolated scotoma; ND: not done; PCC: peripheral concentric contraction; RS: ring scotoma; SAS: superior arcuate scotoma; SIAS: superior and inferior arcuate scotoma; SNAS: superotemporal arcuate scotoma.
At the initial visit, the retina was funduscopically normal in 12 of 14 eyes with AZOOR (Figure
FA showed a normal appearance in 10 eyes (62.5%), retinal vascular wall staining with leakage in 2 eyes (12.5%), and optic disc staining in 2 eyes (12.5%). On ICGA, 4 eyes (28.5%) appeared normal, but patchy hypofluorescence in the macular area or midperiphery was observed in 7 eyes (50.0%). In addition, 7 eyes (50.0%) had diffuse choroidal hyperfluorescence from the posterior pole to the midperipheral region during the middle phase.
The ellipsoid zone in the AZOOR-affected area was invisible in 3 eyes (21.4%), discontinuous in 8 eyes (57.2%), and normal in 3 eyes (21.4%) at the initial visit (Table
Changes in BCVA and the average thresholds at the affected area on Humphrey perimetry in eyes with AZOOR (
Changes in visual functions and subfoveal choroidal thickness in AZOOR and fellow eyes.
Case | Treatment | Best-corrected visual acuity (logMAR) | Average threshold (dB) | Subfoveal choroidal thickness ( | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AZOOR eyes | Fellow eyes | ||||||||||||
Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | ||
1 | None | 0.3 | −0.1 | −0.1 | 15.5 | 30.5 | 29.0 | 45 | 41 | 37 | 33 | 20 | 33 |
2 | None | 0 | −0.1 | 0 | 31.2 | 33.2 | 32.7 | 144 | 123 | 140 | — | — | — |
−0.1 | 0.05 | 0 | 31.7 | 32.2 | 31.0 | 177 | 156 | 169 | — | — | — | ||
3 | None | −0.1 | 0 | 0 | 23.2 | 33.2 | 33.5 | 284 | 251 | 255 | 293 | 280 | 284 |
4 | None | 0.1 | 0 | 0 | 28.7 | 28.5 | 30.2 | 276 | 255 | 255 | — | — | — |
0.1 | 0.1 | 0 | 20.0 | 28.0 | 29.5 | 310 | 289 | 276 | — | — | — | ||
5 | None | 1 | 0.15 | −0.1 | 17.2 | 28.2 | 29.5 | 123 | 99 | 90 | 152 | 169 | 144 |
6 | None | −0.1 | −0.1 | −0.2 | 32.7 | 32.5 | 33.2 | 152 | 148 | 144 | — | — | — |
0.05 | −0.1 | −0.1 | 26.0 | 30.2 | 31.2 | 115 | 107 | 107 | — | — | — | ||
Mean ± SD | 0.13 ± 0.32 | −0.01 ± 0.09 | 0.05 ± 0.06 | 25.1 ± 6.1 | 30.7 ± 2.0 | 30.8 ± 1.6 | 180.6 ± 84.7 | 163.2 ± 78.9 | 163.6 ± 78.1 | 159.3 ± 106.2 | 156.3 ± 106.5 | 153.6 ± 102.6 | |
7 | Steroid pulse | 0.3 | 0.05 | 0.05 | 21.7 | 22.7 | 22.5 | 123 | 107 | 115 | 198 | 198 | 189 |
8 | Steroid pulse | 0.7 | 0.4 | 0.7 | 27.2 | 28.5 | 29.5 | 160 | 152 | 152 | 177 | 206 | 206 |
9 | Steroid pulse | −0.2 | −0.1 | −0.1 | 28.5 | 29.5 | 29.2 | 173 | 156 | 148 | — | — | — |
0 | 0 | −0.2 | 26.0 | 29.2 | 31.0 | 175 | 144 | 148 | — | — | — | ||
10 | Oral PSL, STTA | −0.1 | 0 | 0.05 | 22.7 | 25.2 | 29.2 | 94 | 86 | 82 | 86 | 86 | 82 |
Mean ± SD | 0.14 ± 0.32 | 0.07 ± 0.17 | 0.10 ± 0.31 | 25.2 ± 2.6 | 26.9 ± 2.5 | 28.2 ± 2.9 | 145.0 ± 31.6 | 129.0 ± 27.6 | 129.0 ± 27.0 | 153.6 ± 48.6 | 163.3 ± 54.7 | 159.0 ± 54.8 | |
Total | 0.13 ± 0.32 | 0.01 ± 0.13 | −0.01 ± 0.20 | 25.1 ± 5.1 | 29.3 ± 2.8 | 30.0 ± 2.5 | 167.9 ± 72.6 | 151.0 ± 67.4 | 151.2 ± 66.8 | 156.5 ± 82.6 | 159.8 ± 84.7 | 156.3 ± 82.3 |
Steroid pulse: corticosteroid pulse therapy; PSL: prednisolone; STTA: posterior sub-Tenon injection of triamcinolone acetonide.
In the AZOOR eyes, the mean average thresholds in the affected area at 3 and 6 months were significantly higher than those at baseline (Figure
Changes in average threshold on Humphrey perimetry in eyes with AZOOR and unaffected fellow eyes. The “average threshold” is defined as the average values of 4 threshold points surrounded by a red square shown in Figures
Choroidal thickness changes in the AZOOR eyes and fellow eyes are shown in Tables
Changes in choroidal thicknesses at the sites 1000
Choroidal thickness ( | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Nasal site of the subfovea | Temporal site of the subfovea | |||||||||||
AZOOR eyes | Fellow eyes | AZOOR eyes | Fellow eyes | |||||||||
Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | Baseline | 3 M | 6 M | |
1 | 43 | 43 | 41 | 41 | 35 | 39 | 26 | 20 | 20 | 24 | 26 | 24 |
2 | 103 | 82 | 84 | 134 | 99 | 115 | ||||||
61 | 57 | 57 | 173 | 169 | 169 | |||||||
3 | 328 | 295 | 299 | 328 | 328 | 315 | 295 | 278 | 284 | 286 | 270 | 264 |
4 | 288 | 274 | 272 | 202 | 197 | 202 | ||||||
301 | 301 | 295 | 247 | 253 | 247 | |||||||
5 | 216 | 193 | 177 | 127 | 167 | 136 | 152 | 127 | 117 | 220 | 220 | 210 |
6 | 123 | 123 | 119 | 156 | 165 | 148 | ||||||
138 | 125 | 115 | 152 | 148 | 138 | |||||||
Mean ± SD | 177.8 ± 101.8 | 165.8 ± 97.0 | 162.1 ± 96.9 | 165.3 ± 120.2 | 176.6 ± 119.8 | 163.3 ± 114.3 | 170.7 ± 71.0 | 161.7 ± 73.4 | 160.0 ± 73.7 | 176.6 ± 111.2 | 172.0 ± 105.2 | 166.0 ± 102.8 |
7 | 76 | 66 | 74 | 193 | 205 | 206 | 167 | 152 | 189 | 220 | 220 | 235 |
8 | 142 | 138 | 140 | 140 | 134 | 150 | 146 | 140 | 123 | 177 | 181 | 175 |
9 | 156 | 127 | 111 | 84 | 68 | 63 | ||||||
282 | 224 | 212 | 169 | 156 | 160 | |||||||
10 | 94 | 74 | 61 | 63 | 53 | 72 | 70 | 53 | 63 | 90 | 86 | 84 |
Mean ± SD | 150.0 ± 72.2 | 125.8 ± 56.6 | 119.6 ± 53.9 | 132.0 ± 53.3 | 130.6 ± 62.0 | 142.6 ± 54.9 | 127.2 ± 42.0 | 113.8 ± 44.0 | 119.6 ± 50.7 | 162.3 ± 54.0 | 162.3 ± 56.2 | 164.6 ± 62.0 |
Total | 167.9 ± 93.3 | 151.6 ± 87.0 | 146.9 ± 86.5 | 148.7 ± 94.4 | 153.7 ± 98.1 | 153.0 ± 90.2 | 155.2 ± 65.6 | 144.7 ± 68.5 | 145.6 ± 69.0 | 169.5 ± 87.7 | 167.1 ± 84.5 | 165.3 ± 84.9 |
Changes in choroidal thicknesses using EDI-OCT in eyes with AZOOR and unaffected fellow eyes. (a) In the AZOOR eyes (
Similarly, the choroidal thicknesses at the nasal and temporal sites of the subfovea at 3 and 6 months were significantly lower than baseline values (Table
In the nontreated eyes with AZOOR, values at 3 and 6 months were significantly decreased compared with those at baseline (Figure
In the AZOOR eyes, there was a significant inverse correlation between the changing rates of the average threshold and the SCT at 6 months from baseline (Figure
There was a significant inverse correlation between the changing rates of the average threshold and the SCT during the 6-month follow-up period in AZOOR eyes (
In the present study, by using EDI-OCT during follow-up for eyes with AZOOR, we made the following observations: (1) In both nontreated and corticosteroid-treated AZOOR eyes, the mean average threshold on perimetry in the affected area was significantly increased at 6 months after baseline, with improvement in outer retinal structures, whereas it did not in the unaffected fellow eyes. (2) In the AZOOR eyes, the macular choroidal thicknesses significantly decreased over time compared with baseline, whereas it did not in the unaffected fellow eyes. (3) There was a significant inverse correlation between the changing rates of the average threshold and SCT from baseline to 6 months in the AZOOR eyes.
In the present study, choroidal thickness in AZOOR lesion area significantly decreased with regression of the disease, with a significant correlation between the changes in the visual field impairment and SCT. These results were similar with our previous observations in MEWDS [
In the present study, there were no significant differences in choroidal thicknesses between the AZOOR eyes and the fellow eyes at baseline, although the mean SCT was 11
In choroiditis such as Vogt-Koyanagi-Harada disease and serpiginous choroiditis, choroidal thickness decreased and choroidal blood flow velocity increased with regression of these diseases [
The primary limitations of our study include its retrospective design and the small sample size. In this study, choroidal thickness was manually measured using EDI-OCT B-scan. To overcome this measurement bias, further studies are needed to automatically measure choroidal thickness and volume by using swept-source OCT C-scan. Because of rarity of this disease, both eyes per one patient were used from 4 bilaterally affected cases; however, the statistical significance in SCT changes proved to be still maintained even if only the left eyes from 8 cases (other than cases 7 and 8) were analyzed to avoid any systemic confounders (Friedman’s test,
In AZOOR eyes, choroidal thickness in AZOOR-affected area significantly decreased together with improvements in visual function and outer retinal structure. Furthermore, there was a significant correlation between reduction of choroidal thickness and improvement of visual field defects. These results suggest that choroidal thickness increases at the acute stage of AZOOR. Future studies are needed to further examine the involvement of choroidal thickening in the pathogenesis of AZOOR.
All authors have no financial disclosures. The authors declare that there is no conflict of interest regarding the publication of this paper.